Leukemia Research Vol. 15, No. 7, pp, 627-639, 1991. 0145-2126/91 $3.00 + 0.00 Printed in Great Britain. Pergamon Press plc ABNORMAL LOCALIZATION OF IMMATURE PRECURSORS (ALIP) IN THE BONE MARROW OF MYELODYSPLASTIC SYNDROMES: CURRENT STATE OF KNOWLEDGE AND FUTURE DIRECTIONS M. H. MANGI, J. R. SALISBURY* and G. J. MUFTIt Departments of Haematological Medicine and *Morbid Anatomy, King's College School of Medicine and Dentistry, Denmark Hill, London SE5 8RS, U.K. (Received 21 January 1991. Accepted 27 January 1991) Abstract--It has been suggested that the occurrence of abnormal localization of immature precursors (ALIP) in the bone marrow biopsy (BMB) may be of diagnostic and prognostic significance in myelodysplastic syndromes (MDS). The recognition of ALIP has been based exclusively on bone marrow histological appearances. During the last decade technical advances have led to the widespread use of various immunophenotypic markers for the diagnostic and prognostic purposes which has contributed enormously in understanding the development of haemopoietic cells and the cellular origin of various haematological malignancies. In addition proliferation antigens, growth factors, oncogenes, anti-oncogenes and other biological discoveries have opened new vistas to our knowledge of the normal and neoplastic growth processes. Despite this, the precise nature of ALIP and their significance in relation to the aetiopathogenesis and evolution of MDS remains unclear. Indeed the diagnostic value of ALIP in MDS is debatable. Furthermore, the precise cell lineages which comprise ALIP are not defined. The purpose of this review is to address these issues and to incorporate our new findings on the histological and immunophenotypic characterization of immature cell aggregates. Key words: Abnormal localization of immature precursors (ALIP), bone marrow biopsy (BMB), immunohistochemistry, lectins, monoclonal antibodies, myelodysplastic syndromes (MDS). NORMAL LOCALIZATION OF HAEMOPOIETIC PRECURSORS NORMAL human bone marrow biopsies reveal a spa- tial distribution pattern of haemopoietic cells. The erythropoietic islands and megakaryocytes are associated with marrow sinusoids in the central region of marrow cavities, early granulocytic pre- cursors lie close to endosteal surfaces and the more mature forms are found in the central intertrabecular areas [1--4] (Fig. 1). In contrast to erythroblasts which show a focal pattern of distribution (erythron) during maturation, the maturing granulocytic cells are more or less randomly distributed [4-7]. An explanation for this absence of clustering of granulocytic pre- cursors might be that with increasing maturation granulocytic cells exhibit increasing locomotive activity and so can leave their site of origin and move towards the sinusoids. The nests of erythroblasts and megakaryocytes are usually observed in close proximity of sinusoidal wall, thus obtaining an easy access to the intravascular space [1-7]. The biological t To whom correspondence should be addressed. mechanisms underlying these observations are poorly understood. However, work in murine bone marrow provides supporting evidence for the peritrabecular zone being a fostering area for the early devel- opmental stages of granulopoiesis [8-12]. Secretion of various haemopoietic growth factors from the bone marrow haemopoietic and stromal cells is an area of ongoing research [13] and it is anticipated that future studies may provide insights into the mechanisms underlying the topography of haemopoietic cells within the marrow. 627 ABNORMAL LOCALIZATION OF IMMATURE PRECURSORS (ALIP) Krause [14] observed a distinctive topographic dis- tortion of the bone marrow cells in MDS. There was displacement of progenitor cells from peritrabecular areas towards intertrabecular areas, a bone marrow histological pattern termed clusters of immature cells in MDS. This finding of architectural distortion, in particular with centrally located immature precur- sors, [14] did not receive much attention until Tricot